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4-Phenyl-4-oxo-butanoic acid derivatives inhibitors of kynurenine 3-hydroxylase.
Giordani, A; Pevarello, P; Cini, M; Bormetti, R; Greco, F; Toma, S; Speciale, C; Varasi, M.
Afiliación
  • Giordani A; Pharmacia & Upjohn, Chemistry Dept., Nerviano, Milan, Italy.
Bioorg Med Chem Lett ; 8(20): 2907-12, 1998 Oct 20.
Article en En | MEDLINE | ID: mdl-9873646
Kynurenine 3-hydroxylase (KYN 3-OHase) is a key enzyme in the kynurenine pathway of tryptophan degradation and its inhibition may be an effective mechanism for counteracting neuronal excitotoxic damage. We present here a new class of inhibitors derived from a structure-activity relationship (SAR) study of the benzoylalanine side-chain of 1. 2-hydroxy-4-(3,4-dichlorophenyl)-4-oxobutanoic acid (8) and 2-benzyl-4-(3,4-dichlorophenyl)-4-oxo-butanoic acid (10) emerged as the most interesting derivatives. Enantiospecific synthesis for both enantiomers of 8 and diastereomeric salt resolution for those of 10 were successfully applied.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenilbutiratos / Inhibidores Enzimáticos / Oxigenasas de Función Mixta Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 1998 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenilbutiratos / Inhibidores Enzimáticos / Oxigenasas de Función Mixta Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 1998 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido